8-144514122-G-T

Position:

• chr8-144514122-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000617875.6(RECQL4):​c.1879-15C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,609,134 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0086 (20 hom., cov: 34)
  • Exomes 𝑓: 0.00091 (22 hom.)
• Consequence: RECQL4 ENST00000617875.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.00100

Genes affected

RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-144514122-G-T is Benign according to our data. Variant chr8-144514122-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 94887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00863 (1314/152262) while in subpopulation AFR AF= 0.0306 (1269/41534). AF 95% confidence interval is 0.0292. There are 20 homozygotes in gnomad4. There are 616 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.1879-15C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.1879-15C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004260.4	ENSP00000482313	P1
RECQL4	ENST00000621189.4	c.808-15C>A		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000483145
RECQL4	ENST00000532846.2	c.734-15C>A		splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000476551
RECQL4	ENST00000534626.6	c.248-15C>A		splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000477457

Frequencies

GnomAD3 genomes AF: 0.00862 AC: 1311 AN: 152144 Hom.: 20 Cov.: 34

Gnomad AFR AF: 0.0306

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.00207 AC: 483 AN: 233874 Hom.: 7 AF XY: 0.00145 AC XY: 186 AN XY: 128552

Gnomad AFR exome AF: 0.0326

Gnomad AMR exome AF: 0.000950

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000969

Gnomad OTH exome AF: 0.000352

GnomAD4 exome AF: 0.000910 AC: 1326 AN: 1456872 Hom.: 22 Cov.: 36 AF XY: 0.000763 AC XY: 553 AN XY: 724564

Gnomad4 AFR exome AF: 0.0351

Gnomad4 AMR exome AF: 0.00108

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000990

Gnomad4 OTH exome AF: 0.00150

GnomAD4 genome AF: 0.00863 AC: 1314 AN: 152262 Hom.: 20 Cov.: 34 AF XY: 0.00828 AC XY: 616 AN XY: 74434

Gnomad4 AFR AF: 0.0306

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00396 Hom.: 1

Bravo AF: 0.00992

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 03, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 23, 2017	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 11, 2013

- -

Rothmund-Thomson syndrome type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Baller-Gerold syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35126141; hg19: chr8-145739506;